Hope these help ;-)
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Public release date: 4-Feb-2008
Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Grapefruit compound may help combat hepatitis C infectionMGH study reveals mechanism key to maintaining chronic infection, potential therapy target
A compound that naturally occurs in grapefruit and other citrus fruits may be able to block the secretion of hepatitis C virus (HCV) from infected cells, a process required to maintain chronic infection. A team of researchers from the Massachusetts General Hospital Center for Engineering in Medicine (MGH-CEM) report that HCV is bound to very low-density lipoprotein (vLDL, a so-called "bad" cholesterol) when it is secreted from liver cells and that the viral secretion required to pass infection to other cells may be blocked by the common flavonoid
naringenin.
If the results of this study extend to human patients, a combination of naringenin and antiviral medication might allow patient to clear the virus from their livers. The report will appear in an upcoming issue of the journal Hepatology and has been released online.
"By finding that HCV is secreted from infected cells by latching onto vLDL, we have identified a key pathway in the viral lifecycle," says Yaakov Nahmias, PhD, of the MGH-CEM, the paper's lead author. "These results suggest that lipid-lowering drugs, as well as supplements, such as naringenin, may be combined with traditional antiviral therapies to reduce or even eliminate HCV from infected patients"
HCV is the leading cause of chronic viral liver disease in the United States and infects about 3 percent of the world population. Current antiviral medications are effective in only half of infected patients, 70 percent of whom develop chronic infection that can lead to cirrhosis or liver cancer. Since the virus does not integrate its genetic material into the DNA of infected cells the way HIV does, totally clearing the virus could be possible if new cells were not being infected by secreted virus.
"Identifying the route by which HCV is released from cells introduces a new therapeutic target," says Martin Yarmush, MD, PhD, director of the MGH-CEM and the paper's senior author. "That pathway's dependence on cholesterol metabolism could allow us to interfere with viral propagation to other cells and tissues, using tools already developed for atherosclerosis treatment." Yarmush is the Helen Andrus Benedict Professor of Surgery and Bioengineering at Harvard Medical School (HMS).
Grapefruit's bitter taste is caused the presence of the flavonoid naringin, which is metabolized into naringenin, an antioxidant previously reported to help lower cholesterol levels. Considerable research has suggested that HCV infects liver cells by, in essence, "hitching a ride" onto the natural lipoprotein-cholesterol metabolic pathway. Since earlier evidence has shown that naringenin can reduce secretion of vLDL from liver cells, the researchers examined whether the compound might also lower HCV secretion from infected cells. Their experiments confirmed that naringenin does reduce the secretion of HCV from infected cell lines and showed that the compound inhibits the mechanism for secreting a specific lipoprotein that binds HCV.
"This work presents the possibility that non-toxic levels of a dietary supplement, such as naringenin, could effectively block HCV secretion," says Raymond Chung, MD, MGH director of Hepatology and one of the study authors, "This approach might eventually be used to treat patients who do not respond to or cannot take traditional interferon-based treatment or be used in combination with other agents to boost success rates."
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Chung is an associate professor of Medicine at HMS, and Nahmias is an instructor in Surgery and Bioengineering. Additional co-authors of the Hepatology paper are Jonathan Goldwasser, Monica Casali, PhD, Daan van Poll, MD, MGH-CEM; and Takaji Wakita, MD, Tokyo Metropolitan Institute. The work was supported by grants from the National Institutes of Health and Shriners Hospitals for Children.
Massachusetts General Hospital (
www.massgeneral.org), established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.
http://www.eurekalert.org/pub_releases/2008-02/mgh-gcm020408.php~~~~~~~~~~~~~~~
Grapefruit and medication: A cautionary noteGrapefruit and grapefruit juice are healthful, providing enough vitamin C, potassium, dietary fiber, and other nutrients to earn the American Heart Association's "heart-check" mark. That's the good news. The bad news is that grapefruit juice can interact with dozens of medications, sometimes dangerously.
Doctors are not sure which of the hundreds of chemicals in grapefruit are responsible. The leading candidate is furanocoumarin. It is also found in Seville (sour) oranges and tangelos; although these fruits have not been studied in detail, the guidelines for grapefruit should apply to them as well.
Grapefruit's culprit chemical does not interact directly with your pills. Instead, it binds to an enzyme in your intestinal tract known as CYP3A4, which reduces the absorption of certain medications. When grapefruit juice blocks the enzyme, it's easier for the medication to pass from your gut to your bloodstream. Blood levels will rise faster and higher than normal, and in some cases the abnormally high levels can be dangerous.
A variety of medications can be boosted by grapefruit juice; the table below lists some of the most important along with related drugs that are less likely to be influenced.
Grapefruit juice and medications
Drug category (major uses)
Medications substantially boosted by grapefruit juice
Generic name (Brand name)
Medications that have little or no interaction with grapefruit juice
Generic name (Brand name)
Calcium channel blockers (high blood pressure, angina)
Felodipine (Plendil)
Nifedipine (Procardia, Adalat)
Verapamil (Calan, Isoptin)
Diltiazem (Cardizem)
Amlodipine (Norvasc)
Statins (high cholesterol)
Atorvastatin (Lipitor)
Simvastatin (Zocor)
Lovastatin (Mevacor)
Fluvastatin (Lescol)
Pravastatin (Pravachol)
Rosuvastatin (Crestor)
Immunosuppressants (to prevent rejection of transplanted organs)
Cyclosporine (Sandimmune)
Benzodiazepines (anxiety, insomnia)
Diazepam (Valium)
Triazolam (Halcion)
Midazolam (Versed)
Flurazepam (Dalmane)
Clonazepam (Klonopin)
Other neurological and psychiatric medications
Buspirone (BuSpar)
Sertraline (Zoloft)
Carbamazepine (Tegretol)
Haloperidol (Haldol)
Trazodone (Desyrel)
Zolpidem (Ambien)
It doesn't take much grapefruit juice to boost the levels of drugs that are susceptible. A single glass can produce a 47% reduction of the intestinal enzyme that regulates absorption. And because this effect of the juice wears off slowly, a third of its impact is still evident after 24 hours.
What are the practical implications of this interaction? If you take one of the affected medications, the simplest solution is to switch to orange juice. If you are really hooked on grapefruit juice, though, you can ask your doctor whether you can switch to a related drug that's less vulnerable to the boosting effect. And if that's not possible, you should certainly avoid taking your pills and your juice simultaneously; the more time between the two, the better, and the smaller your glass of juice, the better. If you are on a low or moderate dose of the medication, you can probably get away with an occasional glass of grapefruit juice, but if you are on a high dose, it could be dangerous. That's especially true in the case of calcium channel blockers, which can lower your blood pressure or slow your heart rate excessively
Sildenafil (Viagra) is of special interest to men. The clinical information is incomplete, but men who take Viagra should be aware that grapefruit juice might boost blood levels of the drug. That could be a good thing for some men with erectile dysfunction, but it could trigger headaches, flushing, or low blood pressure.
http://www.health.harvard.edu/fhg/updates/update0206d.shtml~~~~~~~~~~~~~
Grapefruit Juice And Medication Can Be A Dangerous MixScienceDaily (Jan. 26, 2005) — January 18, 2005 -- Grapefruit juice can be dangerous for people on certain medications, nurse researchers remind doctors, nurses, and everyone who takes medicine and enjoys grapefruit juice, in a paper in the American Journal of Nursing, a journal of the American Nurses Association.
Amy Karch, R.N., M.S., of the School of Nursing at the University of Rochester Medical Center reported on a man from a northern climate who moved to Florida for the winter – one of tens of thousands of "snowbirds" who head south each winter – and began drinking two to three glasses of grapefruit juice each day. The man became critically ill as a result of an interaction between grapefruit juice and his cholesterol-lowering medication.
Karch's paper, "The Grapefruit Challenge: The juice inhibits a crucial enzyme, with possibly fatal consequences," appears in the December 2004 issue of the journal.
Interactions between grapefruit juice and medications have long been recognized. Last year, the Medical Letter on Drugs and Therapeutics devoted an entire issue to grapefruit juice and the dangerous drug interactions that can result. The U.S. Food & Drug Administration requires all prospective new drugs that are thought to interact with this enzyme system to be tested for interactions with grapefruit juice. And a warning about grapefruit juice is included in the "food-drug interactions" that come with dozens of medications. Nevertheless, Karch says many health-care professionals and patients don't know about the risk.
"The potential of drug interactions with grapefruit juice has been out there a long time, but most people just aren't aware of it," says Karch, a clinical associate professor of nursing. "There is so much information bombarding people all the time, that a lot of people may have heard this but forgotten it. But the problems can be life-threatening."
The patient profiled in Karch's article had high cholesterol and other risk factors for cardiac disease. The doctor put the patient on atorvastatin (Lipitor), and the patient began dieting and exercising. Two months after the patient went to Florida for the winter, he suddenly had muscle pain, fatigue and fever, and went to the emergency room. The patient ended up going into kidney failure and ultimately died.
The only major change in the person's lifestyle had been that, upon arriving in Florida, he began picking grapefruit off a tree on the patio and drinking two or three glasses of fresh grapefruit juice every day.
Karch, an expert on drug interactions, explains that grapefruit juice is one of the foods most likely to cause problems with drugs, because it is metabolized by the same enzyme in the liver that breaks down many drugs. The cytochrome P-450 3A4 enzyme breaks down grapefruit juice into useful components for body, just like it breaks down dozens of medications. Karch says when the system is overloaded, the grapefruit juice can "swamp" the system, keeping the liver busy and blocking it from breaking down drugs and other substances.
Drugs that use the same pathway and interact with grapefruit juice target some of the most common health problems doctors see today. The list consists of more than 50 medications, including some drugs used to treat high cholesterol, depression, high blood pressure, cancer, depression, pain, impotence, and allergies.
Karch notes that interactions with grapefruit juice are well known and documented among drug researchers, and that an appropriate warning label is included with each prescription. Nevertheless, she says that many patients, nurses and doctors aren't aware of the interactions or the potential serious consequences, and that many people fail to read the warning labels about drug-food interactions.
The consequences of an interaction depend on the drug involved. A person on an anti-depressant might have too much or too little energy, depending on the specific medication. Someone on antibiotics might end up with diarrhea or could be ill longer than usual because the some drugs won't work as well as they should. A heart patient might not get the lowered blood pressure that a medication should deliver, or the heart's rhythms might become irregular if an anti-arrhythmia drug can't do its job. The juice could also affect the effectiveness of a woman's hormone-replacement-therapy medication.
The most severe effects are likely with some cholesterol-lowering medications, Karch says. While the liver devotes its resources to grapefruit juice, the medication could build up to dangerous levels, causing a breakdown of the body's muscles and even kidney failure. This is likely what happened to the patient discussed in the article, Karch says.
To prevent such problems, Karch repeats what doctors and nurses tell their patients every day: Read a medication's warning label carefully. If an interaction with grapefruit juice is possible, the patient should stop drinking the juice until speaking with his or her doctor. In some cases it might be possible to switch a patient to a different drug without the risk; in other cases the patient might simply have to give up grapefruit juice.
She says that more people than usual are vulnerable at this time of year, because losing weight is among the most popular New Year resolutions, and some diets are built around drinking lots of grapefruit juice.
Karch's paper is the latest in a column the journal devotes to "practice errors," where nurses report unusual clinical problems and Karch looks into how widespread the problem might be. Last year she also reported that nurses had found that some types of skin patches could catch on fire when patients receive magnetic resonance imaging (MRI) scans.
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Drugs that Interact with Grapefruit Juice:
(from the December 2004 issue of the American Journal of Nursing)
Antibiotics: clarithromycin, erythromycin, troleandomycin
Anxiolytics: alprazolam, buspirone, midazolam, triazolam
Antiarrhythmics: amiodarone, quinidine
Anticoagulant: warfarin
Antiepileptic: carbamazepine
Antifungal: itraconazole
Anthelmintic: albendazole
Antihistamine: fexofenadine
Antineoplastics: cyclophosphamide, etoposide, ifosfamide, tamoxifen, vinblastine, vincristine
Antitussive: dextromethorphan
Antivirals: amprenavir, indinavir, nelfinavir, ritonavir, saquinavir
Benign prostatic hyperplasia treatment: finasteride
β-blockers: carvedilol
Calcium channel blockers: diltiazem, felodipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil
Erectile dysfunction drugs: sildenafil, tadalafil
Hormone replacement: cortisol, estradiol, methylprednisolone, progesterone, testosterone
Immunosuppressants: cyclosporine, sirolimus, tacrolimus
HMG-CoA reductase inhibitors: atorvastatin, fluvastatin, lovastatin, simvastatin
Opioids: alfentanil, fentanyl, sufentanil
Selective serotonin reuptake inhibitors: fluvoxamine, sertraline
Xanthine: theophylline
http://www.sciencedaily.com/releases/2005/01/050124010803.htm
